 |
PDBsum entry 5ef4
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Structural and functional characterization of the major allergen amb a 11 from short ragweed pollen.
|
|
|
Authors
|
|
R.Groeme,
S.Airouche,
D.Kopečný,
J.Jaekel,
M.Savko,
N.Berjont,
L.Bussieres,
M.Le mignon,
F.Jagic,
P.Zieglmayer,
V.Baron-Bodo,
V.Bordas-Le floch,
L.Mascarell,
P.Briozzo,
P.Moingeon.
|
|
|
Ref.
|
|
J Biol Chem, 2016,
291,
13076-13087.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Allergy to the short ragweed (Ambrosia artemisiifolia) pollen is a major health
problem. The ragweed allergen repertoire has been recently expanded with the
identification of Amb a 11, a new major allergen belonging to the cysteine
protease family. To better characterize Amb a 11, a recombinant proform of the
molecule with a preserved active site was produced in Escherichia coli,
refolded, and processed in vitro into a mature enzyme. The enzymatic activity is
revealed by maturation following an autocatalytic processing resulting in the
cleavage of both N- and C-terminal propeptides. The 2.05-Å resolution crystal
structure of pro-Amb a 11 shows an overall typical C1A cysteine protease fold
with a network of molecular interactions between the N-terminal propeptide and
the catalytic triad of the enzyme. The allergenicity of Amb a 11 was confirmed
in a murine sensitization model, resulting in airway inflammation, production of
serum IgEs, and induction of Th2 immune responses. Of note, inflammatory
responses were higher with the mature form, demonstrating that the cysteine
protease activity critically contributes to the allergenicity of the molecule.
Collectively, our results clearly demonstrate that Amb a 11 is a bona fide
cysteine protease exhibiting a strong allergenicity. As such, it should be
considered as an important molecule for diagnosis and immunotherapy of ragweed
pollen allergy.
|
|
|
|
|
|
|
